Summary
A bioRxiv preprint reports that genetic and drug-based SARM1 inhibition protected axons in mouse models relevant to multiple sclerosis. The drug preserved visual function without preventing demyelination.
A bioRxiv preprint reports that inhibiting SARM1 preserved axons and visual function in mouse models used to study multiple sclerosis (MS). The experiments used genetic approaches and the small molecule 5-iodoisoquinoline (5IIQ); in the experimental autoimmune encephalomyelitis model, the drug’s reported axonal protection occurred without reducing demyelination. The findings are preclinical and do not establish a treatment for people with MS.
What the experiments found
The researchers examined SARM1, a protein involved in programmed axon destruction, using three approaches: mice with SARM1 deleted throughout the body; viral delivery of CRISPR to reduce or increase SARM1 in retinal ganglion cells; and treatment with 5IIQ. They tested these approaches in optic nerve crush, an injury model, and experimental autoimmune encephalomyelitis (EAE), a mouse model of autoimmune disease affecting the central nervous system.
Deleting SARM1 throughout the body did not change the overall clinical course of EAE. The researchers nevertheless reported preserved axons and myelin, alongside changes in peripheral inflammatory cytokines and persistent immune-cell infiltration in the central nervous system. Reducing SARM1 in retinal ganglion cells partially protected those cells and their axons during EAE. Increasing it worsened retinal function and axonal injury.
Treatment with 5IIQ preserved axonal integrity and restored visual function in both models, with visual function assessed by electrophysiology. In EAE, treatment also reduced serum neurofilament light chain (NfL), a marker associated with nerve-cell injury. It did not reduce demyelination.
Why separating axon damage from demyelination matters
MS can damage myelin, the insulating layer around nerve fibres, and also lead to axon loss. Axons transmit signals between nerve cells, so their degeneration can contribute to lasting neurological disability. The study’s results suggest that SARM1-related axon destruction can be targeted separately from the processes causing demyelination: in these mouse experiments, axonal and visual measures improved even though demyelination remained.
The authors propose SARM1 inhibition as a possible neuroprotective complement to treatments aimed at immune activity or remyelination. That is a research direction, not a demonstrated clinical benefit. The evidence comes from mouse models, and the paper is a preprint posted on bioRxiv; whether SARM1 inhibition can protect neurological function in people with MS remains to be tested.